title: Bone morphogenetic protein 9 overexpression reduces osteosarcoma cell migration and invasion.
abstract: Transforming growth factor-β (TGF-β) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-β family expressed in a variety of human carcinoma cell lines. The role of bone morphogenetic protein 9 (BMP9), the most powerful osteogenic factor, in osteosarcoma (OS) progression has not been fully clarified. The expression of BMP9 and its receptors in OS cell lines was analyzed by RT-PCR. We found that BMP9 and its receptors were expressed in OS cell lines. We further investigated the influence of BMP9 on the biological behaviors of OS cells. BMP9 overexpression in the OS cell lines 143B and MG63 inhibited in vitro cell migration and invasion. We further investigated the expression of a panel of cancer-related genes and found that BMP9 overexpression increased the phosphorylation of Smad1/5/8 proteins, increased the expression of ID1, and reduced the expression and activity of matrix metalloproteinase 9 (MMP9) in OS cells. BMP9 silencing induced the opposite effects. We also found that BMP9 may not affect the chemokine (C-X-C motif) ligand 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis to regulate the invasiveness and metastatic capacity of OS cells. Interestingly, CXCR4 was expressed in both 143B and MG63 cells, while CXCL12 was only detected in MG63 cells. Taken together, we hypothesize that BMP9 inhibits the migration and invasiveness of OS cells through a Smad-dependent pathway by downregulating the expression and activity of MMP9.
authors.affiliation: Key Laboratory of Diagnostic Medicine, Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: Zilan
authors.initials: Z
authors.lastname: Lv
authors.forename: Dandan
authors.initials: D
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhan
authors.forename: Peipei
authors.initials: P
authors.lastname: Song
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Huili
authors.initials: H
authors.lastname: Bai
authors.forename: Baolin
authors.initials: B
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Weng
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000235:genetics* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D019718:Receptors, CXCR4 / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D051896:Smad Proteins, Receptor-Regulated / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D019718:Receptors, CXCR4; D051896:Smad Proteins, Receptor-Regulated; D016212:Transforming Growth Factor beta; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9